Clinical Trial: Efficacy of Eltrombopag to Improve Thrombocytopenia of MYH9-related Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Exploratory Phase II Dose Escalation Study of Eltrombopag in MYH9 Related Disease

Brief Summary: The term MYH9-related disease (MYH9RD) includes four genetic disorders: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome. All these disorders derive from mutation of a unique gene, named MYH9, and they have been recognized as different clinical presentations of a single illness that was named MYH9RD. All patients affected by MYH9RD present since birth with thrombocytopenia, which can result in a variable degree of bleeding diathesis; some of them subsequently develop additional clinical manifestations, such as renal damage, sensorineural hearing loss, and/or presenile cataracts. Eltrombopag is an oral thrombopoietin receptor agonist that stimulates proliferation and differentiation of megakaryocytes, the bone marrow cells that produce blood platelets. This drug is effective in increasing platelet count in healthy volunteers, as well as in patients affected by some acquired thrombocytopenias, such as idiopathic thrombocytopenic purpura and HCV related thrombocytopenia. The purpose of this study is to determine if eltrombopag, administered orally at the dose of 50 or 75 mg/daily for up to 6 weeks, is effective in increasing platelet count of patients affected by MYH9RD. Further aims of this study are to test if eltrombopag is effective in reducing bleeding tendency of MYH9RD patients; to evaluate safety and tolerability of eltrombopag in patients with MYH9RD; to evaluate in vitro function of platelets produced during therapy in patients responding to this drug.

Detailed Summary:
Sponsor: IRCCS Policlinico S. Matteo

Current Primary Outcome: Response to Drug Based on Platelet Count at the End of Therapy [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]

The primary endpoints were the achievement of a platelet count over 100 x10e9/L or at least 3 times the baseline value (major response), or at least twice the baseline value but less than major response (minor response). The overall response to therapy is reported. Platelet count was measured at the end of therapy (21 or 42 days, see study design) by phase-contrast microscopy.


Original Primary Outcome: platelet count determined by phase-contrast microscopy [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]

Duration of therapy (21 or 42 days) is determined by patient's platelet count at day 21. Patients with platelet count of 150 x10e9/L or more at day 21 will stop therapy at day 21. Patients with less than 150 x10e9/L platelets at day 21 will continue therapy until day 42 (see intervention).


Current Secondary Outcome:

  • Bleeding Tendency Assessed by WHO Bleeding Score [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]
    The percentage of patients with bleeding diathesis (grade 1, i.e. cutaneous bleeding, or grade 2, i.e. mild blood loss, according to WHO bleeding score) was calculated at baseline and at the end of therapy. The results are expressed as the mean change in the percentage of patients with bleeding diathesis (95%CI).
  • All Types of Adverse Events [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]
    All type of adverse events were registered.Results indicate the number of participants who experience a side effect of the drug.
  • in Vitro Function of Platelets Produced During Therapy in Responding Patients [ Time Frame: 21 days or 42 days of therapy ]
    in vitro platelet function will be assessed in patients achieving a platelet count of 100 x10e9/L or more at the end of the therapy


Original Secondary Outcome:

  • Bleeding Tendency Assessed by WHO Bleeding Score [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]
    Duration of therapy (21 or 42 days) is determined by patient's platelet count at day 21. Patients with platelet count of 150 x10e9/L or more at day 21 will stop therapy at day 21. Patients with less than 150 x10e9/L platelets at day 21 will continue therapy until day 42 (see intervention).
  • All Types of Adverse Events [ Time Frame: 21 days and/or 42 days of therapy, 15 and 30 days after the end of therapy ]
    Duration of therapy (21 or 42 days) is determined by patient's platelet count at day 21. Patients with platelet count of 150 x10e9/L or more at day 21 will stop therapy at day 21. Patients with less than 150 x10e9/L platelets at day 21 will continue therapy until day 42 (see intervention).
  • in Vitro Function of Platelets Produced During Therapy in Responding Patients [ Time Frame: 21 days or 42 days of therapy ]
    in vitro platelet function will be assessed in patients achieving a platelet count of 100 x10e9/L or more at the end of the therapy


Information By: IRCCS Policlinico S. Matteo

Dates:
Date Received: May 28, 2010
Date Started: January 2009
Date Completion:
Last Updated: July 22, 2011
Last Verified: July 2010